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Association of the LRP1 gene and cognitive performance with amnestic mild cognitive impairment in elderly Chinese

Published online by Cambridge University Press:  10 August 2009

Yong M. Shi
Affiliation:
School of Clinical Medicine, Southeast University, Nanjing, China Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, China
Hong Zhou
Affiliation:
School of Clinical Medicine, Southeast University, Nanjing, China Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, China
Zhi J. Zhang*
Affiliation:
School of Clinical Medicine, Southeast University, Nanjing, China Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, China
Hui Yu
Affiliation:
School of Clinical Medicine, Southeast University, Nanjing, China
Feng Bai
Affiliation:
School of Clinical Medicine, Southeast University, Nanjing, China
Yong G. Yuan
Affiliation:
School of Clinical Medicine, Southeast University, Nanjing, China Department of Psychiatry, Nanjing Brain Hospital, Nanjing, China
Ling L. Deng
Affiliation:
School of Clinical Medicine, Southeast University, Nanjing, China
Jian P. Jia
Affiliation:
Department of Neurology, XuanWu Hospital, Capital Medical University, Beijing, China
*
Correspondence should be addressed to: Zhi J. Zhang, M.D., Ph.D., Department of Neurology, affiliated ZhongDa Hospital of Southeast University, No. 87 DingJiaQiao Road, Nanjing, PR China, 210009. Phone: +86–25-83272023; Fax: +86–25-83272023. Email: zhijunzhang838@yahoo.com.cn.

Abstract

Background: The genetic region coding for low-density lipoprotein receptor-related protein1 (LRP1) is considered an intriguing susceptibility locus for Alzheimer's disease (AD). Amnestic mild cognitive impairment (aMCI) is characterized by episodic memory impairment and represents the prodromal stage of AD. Our aim in this study is to investigate the relationship between LRP1 genetic variation and aMCI, and the influence of LRP1 on cognitive performance.

Methods: We performed a case-control association study analyzing five polymorphisms in LRP1 gene by TaqMan Assays-on-Demand SNP Genotyping. All samples were derived from Chinese subjects (109 cases, 104 healthy controls) and assessed using multi-dimension neuropsychological instruments.

Results: We identified haplotypes within the region containing the LRP1 gene. Of these, haplotype TAA (T: rs1800194; A: rs11837145; A: rs10876967) was significantly associated with aMCI, being over-represented in aMCI versus healthy controls. Haplotype TAA was associated with poor performance on episodic memory in all subjects.

Conclusions: This study confirms the association between genetic variants in LRP1 and aMCI. Moreover, we have identified a relationship between LRP1 genetic variation and specific aspects of neurocognitive function. Our convergent results suggest that LRP1 plays an important role in cognitive function and possibly in the pathogenesis of aMCI.

Type
Research Article
Copyright
Copyright © International Psychogeriatric Association 2009

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